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G. B. Reddy, M. N. Mandal, V. Vasireddy, T. Mrudula, X. Wang, M. M. Jablonski, N. V. Giridharan, R. Ayyagari; Photoreceptor Degeneration in a Spontaneous Obese Rat Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4507.
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Studies indicate a strong association between ocular complications and obesity, particularly cataract and retinal dystrophies. The molecular basis through which obesity increases the risk of retinal dystrophies is not yet known. The current study is an attempt to characterize photoreceptor degeneration in a spontaneous obese rodent model, WNIN/Ob rat.
Histology, ultrastructure and immuohistochemistry were performed on sections obtained from the eyes of 2 to 12 months old WNIN/Ob rat and its lean littermates. RNA from retina of 2 and 12 months old WNIN/Ob and its lean littermate rats was used for microarray analysis using Affymetrix Rat Genome 230 2.0 Gene Chip and expression of selected retinal genes was analyzed by real-time PCR analysis.
No obvious change in retinal morphology was observed at 2 months age in obese rat as compared to its littermate lean controls. Onset of retinal degeneration appeared to be between 4-6 months of age. By 12 months age there were noteworthy changes in obese rat retina, particularly significant thinning of outer nuclear layer. Immunohistochemical analysis also indicated photoreceptor degeneration, particularly rod cell loss, in obese rat retina. By microarray analysis we identified 429 genes that were differentially expressed in 12 months obese retina. Most of down-regulated genes (369) were found to be involved in phototransduction and up-regulated genes (60) were related to apoptotic and stress response pathways. RT-PCR analysis of selected retinal genes validated the microarray data and further confirmed photoreceptor degeneration phenotype in WNIN obese rats.
These studies reveal progressive retinal degeneration, specifically rod cell loss, in the selected obese rat model. This model may be thus useful to investigate retinal degeneration associated with obesity. A careful analysis with other phenotypes of WNIN/Ob along with the parental Wistar rats at different ages is underway to corroborate these findings.
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